This project melds the efforts of five interacting research groups. Its general goal is better understanding of the roles of the blood clotting factors, particularly Fs. VIII and IX, in hemostasis and thrombosis. The strategy is to utilize biochemical and biophysical methods to examine the structure and function of Fs. VIII and IX; to examine their antigenic determinants using both hetero- and allo-polyclonal-antibodies, and monoclonal antibodies raised against entire factors as well as various fragments; to study the assembly of F. VIII in endothelial cells utilizing the methods of somatic cell genetics; and to clone the gene for canine F. IX utilizing the methods of molecular biology. These research programs are closely related to the large in-patient and out-patient services of the NC Memorial Hospital which are concerned with treating patients having disorders of hemostasis and thrombosis. An intimate relation exists between these clincal services and the research programs of the proposed project, and there will be collaborative research involving the basic scientists and clinicians.